{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:20:46Z","timestamp":1793874046927,"version":"4.6.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>To identify novel markers and signaling pathways for early onset preeclampsia, we profiled human maternal-fetal interface units (fetal villi and maternal decidua) from early onset preeclampsia and healthy controls using single-nucleus RNA sequencing combined with spatial transcriptomics. The placental syncytiotrophoblast is in direct contact with maternal blood and forms the barrier between fetal and maternal circulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We identified different transcriptomic states of the endocrine syncytiotrophoblast nuclei with patterns of dysregulation associated with a senescence-associated secretory phenotype and a spatial dysregulation of senescence in the placental trophoblast layer. Elevated senescence markers were validated in placental tissues of clinical multicenter cohorts. Importantly, several secreted senescence-associated secretory phenotype factors were elevated in maternal blood already in the first trimester. We verified the secreted senescence markers, PAI-1 (plasminogen activator inhibitor 1) and activin A, as identified in our single-nucleus RNA sequencing model as predictive markers before clinical preeclampsia diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This indicates that increased syncytiotrophoblast senescence appears weeks before clinical manifestation of early onset preeclampsia, suggesting that the dysregulated preeclamptic placenta starts with higher cell maturation resulting in premature and increased senescence-associated secretory phenotype release. These senescence-associated secretory phenotype markers may serve as an additional early diagnostic tool for this syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.23362","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T05:01:26Z","timestamp":1729659686000},"page":"787-799","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Senescent Syncytiotrophoblast Secretion During Early Onset Preeclampsia"],"prefix":"10.1161","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6385-2866","authenticated-orcid":true,"given":"Olivia","family":"Nonn","sequence":"first","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.)."},{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., D.N.M., R.D., F.H.)."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (O.N., D.S.V., J.N., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., F.C., D.N.M., R.D., F.H.)."},{"name":"German Center for Cardiovascular Research (DZHK), Berlin, Germany (O.N., D.S.V., H.B., N.H., K.K., S.K., D.N.M., R.D.)."},{"name":"Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center (O.N., K.S., T. Kroneis, L.N., D.F., B.H., A.E.-H., M.G.), Medical University of Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Debnath","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Digital Health, Germany (O.D., S. Tiesmeyer, P.K., A.M., N.M.-B., R.E., N.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1309-5147","authenticated-orcid":true,"given":"Daniela S.","family":"Valdes","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.)."},{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., D.N.M., R.D., F.H.)."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (O.N., D.S.V., J.N., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., F.C., D.N.M., R.D., F.H.)."},{"name":"German Center for Cardiovascular Research (DZHK), Berlin, Germany (O.N., D.S.V., H.B., N.H., K.K., S.K., D.N.M., R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Sallinger","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center (O.N., K.S., T. Kroneis, L.N., D.F., B.H., A.E.-H., M.G.), Medical University of Graz, Austria."},{"name":"Centre for Biomarker Research in Medicine, Graz, Austria (K.S., T. Kroneis, A.E.-H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-2852","authenticated-orcid":true,"given":"Ali Kerim","family":"Secener","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center - Berlin Institute for Medical Systems Biology (MDC-BIMSB), Berlin, Germany (A.K.S., C.F.)."},{"name":"Department of Biology, Chemistry and Pharmacy, Institute of Chemistry and Biochemistry, Freie Universit\u00e4t Berlin, Germany (A.K.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0329-2435","authenticated-orcid":true,"given":"Cornelius","family":"Fischer","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center - Berlin Institute for Medical Systems Biology (MDC-BIMSB), Berlin, Germany (A.K.S., C.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-1523","authenticated-orcid":true,"given":"Sebastian","family":"Tiesmeyer","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Digital Health, Germany (O.D., S. 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Kuenzer), Medical University of Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.)."},{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., D.N.M., R.D., F.H.)."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (O.N., D.S.V., J.N., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., F.C., D.N.M., R.D., F.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-8479","authenticated-orcid":true,"given":"Theresa","family":"Maxian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Austria (T.M., M.K., S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kn\u00f6fler","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Medical University of Vienna, Austria (T.M., M.K., S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-1975","authenticated-orcid":true,"given":"Philipp","family":"Karau","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Digital Health, Germany (O.D., S. Tiesmeyer, P.K., A.M., N.M.-B., R.E., N.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4288-3828","authenticated-orcid":true,"given":"Hendrik","family":"Bartolomaeus","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.)."},{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., D.N.M., R.D., F.H.)."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (O.N., D.S.V., J.N., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., F.C., D.N.M., R.D., F.H.)."},{"name":"German Center for Cardiovascular Research (DZHK), Berlin, Germany (O.N., D.S.V., H.B., N.H., K.K., S.K., D.N.M., R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4761-9340","authenticated-orcid":true,"given":"Thomas","family":"Kroneis","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center (O.N., K.S., T. Kroneis, L.N., D.F., B.H., A.E.-H., M.G.), Medical University of Graz, Austria."},{"name":"Centre for Biomarker Research in Medicine, Graz, Austria (K.S., T. 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Kroneis, L.N., D.F., B.H., A.E.-H., M.G.), Medical University of Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Haase","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.)."},{"name":"Experimental and Clinical Research Center, a cooperation between the Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association and the Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., D.N.M., R.D., F.H.)."},{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (O.N., D.S.V., J.N., J.U., H.B., A.F., N.H., K.K., S.K., R.S.-U., F.C., D.N.M., R.D., F.H.)."},{"name":"German Center for Cardiovascular Research (DZHK), Berlin, Germany (O.N., D.S.V., H.B., N.H., K.K., S.K., D.N.M., R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Malt","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Digital Health, Germany (O.D., S. Tiesmeyer, P.K., A.M., N.M.-B., R.E., N.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5103-7282","authenticated-orcid":true,"given":"Niklas","family":"M\u00fcller-B\u00f6tticher","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health at Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Center of Digital Health, Germany (O.D., S. 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